Published findings of intravenous nicotine self-injection indicate that the reinforcing properties of nicotine are weak when the drug is made available according to continuous reinforcement (CRF) or fixed-ratio (FR) schedules. CRF self-injection rates are generally only 2-3 times saline control levels and self-injection frequency is largely insensitive to changes in unit dose. In contrast, drugs of the psychomotor stimulant, opiate, and sedative-hypnotic classes, with similar pharmacokinetic parameters, maintain much higher self-injection rates and show systematic changes in rate with unit dose variations. Recent studies using interval and second-order schedules of nicotine presentation have been more successful in maintaining higher rates of self-administration behavior. Systematic dose-response functions have also been found under these conditions. Food-deprivation, species and strain differences, circadian rhythms, and duration of exposure to the drug also appear to be important variables in determining self-injection rate. Finally, the rapid development of tolerance to the effects of nicotine may account for changes in the pattern of self-administration within daily sessions and the differential sensitivity of those patterns to nicotine pretreatment.