Anal cancer has been hypothesized to be associated with a sexually transmitted agent and, more recently, with the epidemic of human immunodeficiency virus (HIV). The authors used a descriptive incidence study to evaluate these hypotheses based on US data from the Surveillance, Epidemiology, and End Results (SEER) program for 1973-1989 and from the Connecticut Tumor Registry for 1940-1988. Since 1960, anal cancer incidence in Connecticut increased 1.9-fold among men and 2.3-fold among women. Based on information from SEER, the incidence was lowest among white men (1973-1989 average: 0.41/100,000) and highest among black women (1973-1989 average: 0.74/100,000). Residents of the metropolitan areas had a twofold risk of anal cancer compared with populations in less densely populated areas. The most dramatic change in incidence was observed for white men in the San Francisco Bay area, among whom the incidence increased from 0.5/100,000 in 1973-1975 to 1.2/100,000 in 1988-1989 (p trend < 0.001). The relative risks (95% confidence intervals) of anal cancer among never married men compared with ever married men in the urban areas rose from 5.8 (0.9-8.7) in 1973-1978 to 6.7 (4.7-9.5) in 1979-1984 and 10.3 (7.5-14.1) in 1985-1989 (p trend = 0.02). No significant difference was observed among women. In conclusion, anal cancer incidence in the United States has increased significantly during the past 30 years and is now higher in women than men, in blacks than whites, and in residents of metropolitan rather than rural areas. Some of this changing pattern clearly relates to the period prior to the acquired immunodeficiency syndrome (AIDS) epidemic and argues that behavioral changes are important in anal cancer development. However, the recent remarkable change in rates among never married men and men living in the San Francisco Bay area suggests that homosexual men are at special and increasing risk. The authors speculate whether part of this recent increase could be attributed to the AIDS epidemic.