Rheumatic manifestations of substance abuse are uncommon but recognized complications. Repeated injections of drugs and adulterants represent repeated antigenic challenge. The population at greatest risk is that of young males, although females with eating disorders are more apt to develop myopathy, clubbing, or periostitis. Alcohol, the most common substance abused, is associated more often with myopathy. In IV drug abusers, hepatitis B viral infection, bacterial endocarditis, primary skeletal infections, and venous complications are most common in that order. However, the spectrum may evolve as the pattern of substance abuse changes. First, the frequency of cocaine dependence is rapidly approaching that of alcohol. Two regular cocaine users are reported as having Raynaud's phenomenon and abnormal serologies. 61 Second, synthesis of lookalike drugs may produce new associations, such as parkinsonism after IV N-methyl-4-phenyl-l,2,3, 6-tetrahydropyridine. 124,125 Third, the increased use of ipecac and purgatives in eating disorders is an important consideration in young women with otherwise unexplained myopathy or arthritis. 33–39,52–55 Finally, patients with AIDS are presenting with autoimmune phenomena or a spectrum of unusual infections that change as the epidemic evolves. 102–113,123 Increased recognition of these symptom complexes may lead to earlier, more accurate diagnoses and avoidance of unnecessary diagnostic evaluations and delays in treatment.