This study examined the possible association between melanoma and exposure to fertility drugs, specifically clomiphene citrate, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A cohort of 3186 women who attended a fertility clinic between 1 January 1980 and 31 December 1990 was studied; by January 1996, 14 women had been diagnosed with primary melanoma. Details of fertility treatment were extracted from the clinical records. The incidence of melanoma in the cohort resembled that of the female Queensland population (standardized incidence ratio = 0.89, 95% confidence interval [CI] = 0.54-1.48). Exposure to clomiphene citrate, HMG or HCG did not affect the incidence of melanoma. Women with infertile partners who were treated with fertility drugs were at increased risk of melanoma (odds ratio [OR] = 3.17, 95% CI = 1.01-9.98). Compared with women exposed only to clomiphene citrate and HMG, a lower incidence of melanoma was observed among those who received HCG as well (OR = 0.10, 95% CI = 0.02-0.42). Women exposed to two or more cycles of either clomiphene citrate (OR = 0.27, 95% CI = 0.08-0.94) or HMG (OR = 0.23, 95% CI = 0.07-0.84) had a significant reduction in melanoma risk compared with women exposed to no or one cycle. In summary, a woman's infertility per se was not found to be associated with melanoma, while exposure to fertility drugs was positively associated with melanoma in women with infertile partners and negatively associated in women with low doses of fertility drugs.