In a case-control study conducted in Latin America, the relationship of injectable contraceptive (IC) use to risk of invasive cervical cancer was analyzed while controlling for a variety of other risk factors, including female and spouse sexual behavior and infection with human papillomaviruses (HPV). Thirty-two cases and 82 controls reported ever having used IC. Women reporting use of IC for less than 5 years had an adjusted RR of 0.5 (95% Cl = 0.3-0.9), but users for 5 or more years had an RR of 2.4 (95% Cl = 1.0-5.7). The effect of prolonged IC use was stronger for women reporting first use 10 or more years before interview (adjusted RR = 3.4, 95% Cl = 1.1-24.9) and more than 5 years since last use (adjusted RR = 5.3, 95% Cl = 1.1-10.0). Cervical cancer risk associated with prolonged IC use was particularly high among women who reported never having had a Pap smear or having had one 2 or more years before interview (adjusted RR = 6.3, 95% Cl = 2.1-18.7). The reduced cervical cancer risk associated with short-term use of IC may reflect intensive Pap smear screening as the method is initiated. Although hampered by small numbers, these results suggest an adverse effect of prolonged IC use on cervical cancer risk, particularly among women who cease participation in screening programs after terminating usage, and indicate that long-term IC users should be monitored for cervical disease until more conclusive results are available.