The relationship between ego functioning and acute adverse reactions to psychoactive drugs was examined using retrospective data. The data were consistent with a causal model in which characteristic use of regression (and to a lesser extent repression) was associated with acute adverse reactions to marijuana and to LSD. Regression also had an indirect effect through increased usage of LSD. Subjects characterized by the use of intellectualization and denial were less likely to report developing acute adverse reactions. A higher score on a general measure of coping was related to avoiding acute adverse reactions to LSD, but not to marijuana. Projection, regression in the service of the ego, and tolerance of ambiguity has no effect on acute adverse reactions.