A population-based case-control study of 74 women with lip cancer diagnosed from 1978 to 1985 in Los Angeles County (California, United States) and frequency matched to 105 controls investigated the risk of solar radiation and protection from lip sunscreening agents to explore the hypothesis that excess incidence of lip cancer seen in men is due partly to lower rates in women, conferred by frequent use of lip protection. We confirm the importance in women of risk factors similar to those found in men, i.e., fair complexion, sun exposure, and smoking. Risk was related strongly to lifetime solar radiation (odds ratio [OR] = 13.5 for highest quartile of exposure, 95 percent confidence interval [CI] = 4.5-40.6, P trend < 0.0001) and time spent outdoors (OR = 4.7 for highest quartile of average yearly hours, CI = 1.9-12.1, P trend = 0.01). Further, among women with high lifetime solar-radiation exposure, those who used lip protection once a day or less had twice the risk of lip cancer than women who used lip protection more than once a day (OR = 7.3, CI = 1.9-27.2 cf OR = 3.2, CI = 1.1-9.2). These findings show that solar radiation is a major risk factor for lip cancer and suggest that lip sunscreening is protective, thereby supporting the hypothesis that use of lipstick and other sunscreening agents by women has contributed to their lower incidence of this disease.