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As a biological phenomenon the interaction between drugs may be viewed in `explanatory' or `empirical' terms. In clinical psychopharmacology the former is rarely possible: two examples are cited, one concerning amphetamine and reserpine, the other desmethyl-imipramine and tetrabenazine. Among centrally acting substances, empirical studies of the interaction between alcohol and the barbiturates have been pursued intensively by several methods in clinic and laboratory. Both general considerations and recent work on the effects of amphetamine-barbiturate combinations suggest caution in the medical use of mixtures of psychotropic drugs. Adverse reactions caused by interaction between psychotropic drugs and other substances have still to be studied systematically as a potential hazard.