UCHIME is a new program designed to detect chimeric sequences with two or more segments, which are often formed during polymerase chain reaction (PCR) amplification. The program can use a database of chimera-free sequences or detect chimeras de novo by exploiting abundance data. UCHIME outperforms previous methods, such as ChimeraSlayer and Perseus, in terms of sensitivity, especially with short, noisy sequences. In testing on artificial bacterial communities with known composition, UCHIME's de novo sensitivity is comparable to Perseus, but it is over 100 times faster than Perseus and over 1000 times faster than ChimeraSlayer. UCHIME can handle different sequence types and offers both reference and de novo modes, making it a robust and efficient tool for chimera detection in various sequencing contexts.UCHIME is a new program designed to detect chimeric sequences with two or more segments, which are often formed during polymerase chain reaction (PCR) amplification. The program can use a database of chimera-free sequences or detect chimeras de novo by exploiting abundance data. UCHIME outperforms previous methods, such as ChimeraSlayer and Perseus, in terms of sensitivity, especially with short, noisy sequences. In testing on artificial bacterial communities with known composition, UCHIME's de novo sensitivity is comparable to Perseus, but it is over 100 times faster than Perseus and over 1000 times faster than ChimeraSlayer. UCHIME can handle different sequence types and offers both reference and de novo modes, making it a robust and efficient tool for chimera detection in various sequencing contexts.