Aims. To measure the current prevalence of different routes of heroin administration among users and to describe the most frequent patterns in the evolution of the main route from the time of first use to the present and their implications for the control of the HIV epidemic. Design. Cross-section study. Face-to-face interviews using a structured questionnaire. Setting and participants. Nine hundred and nine regular heroin users from Madrid, Barcelona and Seville (about 300 per city), half of them recruited in treatment centres and the other half out of treatment. Measurements. Socio-demographic characteristics, current and historical behaviours related to route of administration. Findings. Before 1980 injection was the first main route of heroin administration for most users in Barcelona and Madrid; in Seville smoking already predominated, although 40% of users began by injecting. Sniffing subsequently became predominant in Barcelona, while smoking became the predominant first route in Madrid and Seville (smoking has been the only first route in Seville since 1991). The prevalence of injection as the main route of administration during the last 30 days was 77.3% in Barcelona, 24.3% in Madrid and 23.9% in Seville; smoking predominated in the latter two cities. The factors most strongly associated with injection as the preferred route were city of recruitment and having a partner who injected. Some 73% of those who stopped injecting in their last change of route stated that the results of their HIV test or fear of becoming infected had been important in making this decision. Conclusions. The change from injecting to smoking will greatly facilitate the control of HIV infection in Spain. However, the main causal factor does not appear to be the perception of HIV risk, but rather other, ecological factors (cultural or market-related). The absence of these factors in some areas may impede the spread of smoking.