The biological significance of sister chromatid exchanges (SCE) and their relationship to mutagenesis is being investigated. DNA postreplication repair, SCE, DNA breaks and mutagenesis were determined in Chinese hamster V79 cells treated with direct-acting chemical and physical mutagens. Dose-response curves showed that benzo(a)pyrene diol-epoxide-I was more potent as a mutagen and also produced a higher frequency of SCE in V79 cells than did benzo(a)pyrene diol-epoxide-II. However, cis- and trans-diaminodichloro-P (II) produced the same frequency of SCE in V79 cells, but only the cis compound was mutagenic. This suggests that SCE may not be directly related to mutagenesis. Caffeine alone does not: 1) alter the frequency of SCE; 2) inhibit DNA postreplication repair; 3) cause DNA breaks; or 4) cause an increase in mutations of V79 cells. When V79 cells were treated with both benzo(a)pyrene diol-epoxide-I and caffeine, the cytotoxic effects were synergistic and DNA postreplication repair was inhibited. However, synergistic effects on either frequency of SCE or frequency of mutation were not detected.