The neurological complications observed in 6 HIV negative intravenous drug users are reported. Four developed acute neuromuscular involvement in a lumbosacral or brachial distribution with rhabdomyolysis, myoglobinuria, hypovolemia, renal and hepatic failure in the 3 most severely affected patients. Despite evidence of immunologic abnormalities and especially presence of anti-heroin antibodies, we feel that causative mechanisms include mixed compression and ischemia with an underlying toxic myopathy, resulting in segmental myopathy with secondary compression of peripheral nerves. Two patients developed myelopathy with acute or chronic onset. The mechanisms were vascular with spinal cord infarction in the acute form and probably infectious with secondary compressive arachnoiditis in the chronic form. In these 2 patients with myelopathy, outcome was poor.