While a burgeoning literature has investigated drug use “careers,” few studies offer insights into the initiation process of illicit drug use. The current study specifically investigated initiation into cannabis and hard drug use using data from three separate surveys conducted in Israel in 1989, 1992, and 1995. Respondents, approximately 12,500, were Jews age 20 to 40; information was elicited concerning consumption of cigarettes, alcohol, and illicit drugs during the last week, last month, last year, and ever. It was hypothesized that there would be two sub-populations: (1) those who are “immune” to drug use and will never use them, and (2) those who are “susceptible” to drug use and for whom drug use is inevitable. Competing hypotheses were tested concerning the determination of susceptibility to drug use and the timing of initiation. A long-term survivor model was employed to permit the empirical distinction between the immune and susceptible populations. Results of statistical analysis indicated that smoking cigarettes did not significantly impact immunity to drug use, but did seem to affect the timing of drug use initiation for both cannabis and hard drugs; cigarette use sped up cannabis initiation for the susceptible group. The findings suggest that anti-smoking campaigns may delay drug initiation, but will do little to affect immunity to drug use. The current model also indicates that drug use immunity is not randomly distributed across the population; some groups experience a higher propensity to use drugs than others. One example is that women tend to have a higher immunity to cannabis initiation than men. Limitations of research include its reliance on self-report data and the use of retrospective initiation data. Future studies should focus on distinguishing between acquired and natural immunity. Tables, references