Under the specific conditions reported for the separate tests Δ9-tetrahydrocannabinol (THC) did not elicit a mutagenic response in microbial and eukaryotic in vitro test systems. THC treatment to histidine auxotrophs of Salmonella typhimurium strains TA 98 (susceptible to frame shift mutation) and TA 100 (susceptible to base pair substitution) were investigated. Analysis for possible revertance in the presence and absence of S9 microsomal activation system indicated an absence of induction of gene mutation. Cultured fibroblasts from healthy individuals and DNA repair deficient Xeroderma pigmentosum patients display similar survival activity upon exposure to THC. There was no observable increase in the number of chromosome breaks or chromatid exchanges following exposure to THC or THC plus S9 microsomal fraction. THC, 11-OHΔ9-THC, cannabinol, and cannabidiol did not induce unscheduled DNA repair synthesis in cultured human fibroblasts. Moreover, THC did not suppress UV-induced DNA repair synthesis.