Effect of caffeine on the frequency of 8-azaguanine (8AG) resistant mutation in Chinese hamster cells (V79 cells) treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was investigated. The results showed that the effects of caffeine appeared to be different in manner depending on the time and duration of caffeine exposure after MNNG treatment. (1) When the cells were exposed to caffeine during the first half of mutation expression time (0-24h after MNNG treatment), the mutation frequency was slightly enhanced compared with MNNG treatment alone. (2) On the contrary, mutation frequency was reduced if caffeine was present during the latter half of expression time (24-48h after MNNG treatment). (3) Caffeine drastically reduced the frequency of mutation if the cells were exposed to caffeine for the whole mutation selection period from 48 to 240h after MNNG treatment.