Octamethylcyclotetrasiloxane (OMCTS; CAS No. 556-67-2) was evaluated in a genetic toxicity battery. In preincubation tests with Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538, no mutagenicity was detected (maximum dose = 5 mg/plate) with or without S9 in two independent trials. Treatment of cultured Chinese hamster ovary (CHO) cells was limited by cytotoxicity at OMCTS concentrations greater than 0.003 mg/mL without S9 and 0.03 mg/mL with S9. CHO cells treated with up to 0.003 mg/mL without S9 and 0.03 mg/mL with S9 showed no significant dose-related increases in chromosomal aberration frequencies. No significant dose-related increases in sister chromatid exchanges (SCEs) occurred in OMCTS-treated CHO cells (maximum OMCTS concentration = 0.003 mg/mL without S9; 0.03 mg/mL with S9). Therefore, OMCTS was concluded to be negative in the SCE assay. In a screen for in vivo clastogenic potential, Sprague-Dawley rats received 700 ppm OMCTS by whole-body vapor inhalation 6 hr daily for 5 days. A negative control group received filtered air on the same schedule. A positive control group was exposed to filtered air on the same schedule and received cyclophosphamide 24 hr before termination. The OMCTS-treated animals were terminated 6 and 24 hr after the final exposure. Positive and negative control animals were terminated 24 hr after the last exposure. No significant, treatment-related increases in chromosomal aberrations were detected. The results of these studies indicate that OMCTS does not possess significant in vitro genotoxic potential. No adverse genetic findings were seen in the in vivo screen for chromosome aberrations.