Caffeine is an environmental agent to which people are commonly exposed through medicines, drinks, food items, etc. It has been shown to be mutagenic in a number of test systems. In addition, it has also been shown to modify the mutagenic response of ionizing radiation, UV, and several chemical mutagens in a number of test systems. We have studied the effect of caffeine on gamma radiation and 4-Nitroquinoline 1-oxide (4-NQO)-induced gene conversion in the yeast Saccharomyces cerevisiae D7. Stationary phase cells were either exposed to 100-600 Gy of 60Co gamma radiation or treated with 0.15-0.3 microM 4-NQO (30 degrees C, 1 hour), after which they were plated on synthetic complete or minimal media with or without caffeine. Caffeine concentrations ranged from 5 to 15 mM. The results indicated that caffeine at 5 and 10 mM decreased gamma radiation-induced gene conversion frequencies significantly at 400 and 600 Gy. At 600 Gy, the decrease was about 30% and 50% with caffeine concentrations of 5 and 10 mM, respectively. In contrast, caffeine was found to increase the induced gene conversion frequency when cells treated with 0.15, 0.225, and 0.3 microM 4-NQO were plated on media containing caffeine. The increase with 5, 10, and 15 mM caffeine was approximately 1.5, 2, and 2.5, respectively, times the value of 4-NQO alone. The results indicate that the posttreatment repair processes following gamma irradiation or 4-NQO treatment are modified via different pathways.