To determine whether the long-acting progestational contraceptive, depot-medroxyprogesterone acetate (DMPA), alters risk of cervical cancer, a hospital-based case-control study was conducted in two hospitals in Bangkok, Thailand, and in one hospital each in Chiang Mai, Thailand, Mexico City, Mexico, and Nairobi, Kenya. Information on prior use of DMPA, screening for cervical cancer, and the suspected risk factors for this disease was ascertained from interviews of 2,009 women with invasive squamous cell cervical cancer and 9,583 controls. For selected subsets of these women, a smoking history was also elicited, blood specimens were collected for measurement of antibodies against herpes simplex and cytomegaloviruses, and information on sexual behavior was obtained from interviews with their husbands. The relative risk (and 95% confidence interval) of invasive squamous cell cervical carcinoma in women who ever used DMPA was estimated to be 1.11 (0.96, 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed. These results provide reassurance that prolonged use of DMPA does not enhance risk of invasive squamous cell cervical carcinomas, even after a potential latent period of over a decade.