Despite the fairly large literature that developed during the past 15 years or so, the effect of cannabinoids on the immune system is still unsettled. The evidence has been contradictory and is more supportive of some degree of immunosuppression only when one considers in vitro studies. These have been seriously flawed by the very high concentrations of drug used to produce immunosuppression and by the lack of comparisons with other membrane-active drugs. The closer that experimental studies have been to actual clinical situations, the less compelling has been the evidence. Although the topic was of great interest during the 1970's, as indicated by the preponderance of the references from that period, interest has waned during the present decade. This waning of interest suggests that perhaps most investigators feel that this line of inquiry will not be rewarding. The AIDS epidemic has also diverted the attention of immunologists to the far more serious problem of the truly devastating effects a retrovirus can have on a portion of the immune system. The relationship between the use of social drugs and the development of clinical manifestations of AIDS has been of some interest, however. Persons infected with the virus but not diagnosed as AIDS have been told to avoid the use of marijuana and/or alcohol. This advice may be reasonable as a general health measure, but direct evidence that heeding this warning will prevent the ultimate damage to the immune system is totally lacking.