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Objectives. In Spain the number of new acquired immunodeficiency syndrome (AIDS) cases among injection drug users continues to rise. The time trend up to 1994 has been analyzed, with special attention paid to die different generations. Methods. The source for injection drug use-related cases was the Spanish AIDS Register Independent analyses of annual specific rates were run for each sex with the use of an age-period-cohort log-linear model. Results. After adjustment for age and year of diagnosis, AIDS incidence related to injection drug use is associated with specific birth cohorts. Rising values are observed in the successive generations born during the 1950s, peaking in men born in 1962 and women born in 1964. In subsequent cohorts, there is a marked falloff in incidence for both sexes, but this decline is seen to halt in men from the 1972 birth cohort onwards. The overall period effect is upward, yet the trend flattens in the last years. There is a pronounced age effect with maximum values in men and women at ages 29 and 27, respectively. Conclusions. It is essential to urge avoidance of risk behaviors in new generations. (Am J Public Health. 1997;87:770-774)