The objective of this study was to determine what sociodemographic, lifestyle, or drug-related characteristics predict temporal changes in self reported drug injection frequencies among HIV-seronegative injection-drug users (IDUs) who were being given HIV testing and risk reduction counseling. The 277 subjects were given 4-11 quarterly interviews including detailed history of drug use and other HIV risk factors, HIV risk reduction counseling, and venipuncture for HIV antibody testing. A regression slope of change over time in drug injection frequency was calculated for each subject, and categories were created of decreasing temporal slope, increasing slope, relapse (decrease initially, then increase), or no substantial change. Only 44% of subjects decreased their drug injection frequencies despite repetitive HIV testing and counseling. In multivariate logistic analyses, decreasing temporal trends were associated with consistent enrollment in methadone maintenance (p < .1), whereas increasing trends conversely were associated with inconsistent enrollment (p < .01) and also with an absence of crack use (p < .01). Relapses were significantly associated with needle sharing with multiple partners and a low frequency of smoking. The data suggest that methadone maintenance facilitates a positive response to HIV risk reduction counseling. However, the fact that only a minority of subjects displayed a decreasing temporal trend in drug injection frequencies emphasizes the need for improved therapeutic and counseling techniques.