Macrophages release mitogenic substances that enhance the response of T lymphocytes to mitogens like phytohemagglutinin (PHA), but do not stimulate B cells in the absence of T cells. These factors are significantly increased by agents such as endotoxin. The study shows that human supernatants (SUP) from peripheral blood lymphocytes can potentiate the response of mouse thymocytes to PHA, and also enhance the response of spleen cells to PHA and concanavalin A (Con A). The effect of SUP is independent of the presence of macrophages and is not due to carryover of mitogen from the donor culture. SUP also enhances the response of purified human lymphocytes to PHA. The study suggests that the mitogenic activity is due to a soluble factor, termed lymphocyte-activating factor (LAF), which is released by macrophages and enhances the response of T cells to various mitogens. LAF is effective on both central and peripheral T cells, and enhances their responses to other stimulants. The study also shows that LAF does not affect the response of spleen cells to lipopolysaccharide (LPS), which stimulates B cells. The data suggest that T cells respond differently to LAF and PHA, and that this may be due to differences in the number of receptor sites for particular stimulants on individual cells. The study concludes that LAF is a soluble factor released by macrophages that enhances the response of T cells to various mitogens.Macrophages release mitogenic substances that enhance the response of T lymphocytes to mitogens like phytohemagglutinin (PHA), but do not stimulate B cells in the absence of T cells. These factors are significantly increased by agents such as endotoxin. The study shows that human supernatants (SUP) from peripheral blood lymphocytes can potentiate the response of mouse thymocytes to PHA, and also enhance the response of spleen cells to PHA and concanavalin A (Con A). The effect of SUP is independent of the presence of macrophages and is not due to carryover of mitogen from the donor culture. SUP also enhances the response of purified human lymphocytes to PHA. The study suggests that the mitogenic activity is due to a soluble factor, termed lymphocyte-activating factor (LAF), which is released by macrophages and enhances the response of T cells to various mitogens. LAF is effective on both central and peripheral T cells, and enhances their responses to other stimulants. The study also shows that LAF does not affect the response of spleen cells to lipopolysaccharide (LPS), which stimulates B cells. The data suggest that T cells respond differently to LAF and PHA, and that this may be due to differences in the number of receptor sites for particular stimulants on individual cells. The study concludes that LAF is a soluble factor released by macrophages that enhances the response of T cells to various mitogens.