Phosphorus magnetic resonance spectroscopy (31P MRS) at 1.5 T was performed on nine polysubstance abusing men. All nine patients met DSM-III-R criteria for concurrent cocaine and heroin dependence, were neurologically normal, were negative for the human immunodeficiency virus, and had normal clinical brain MRI scans. Patients were scanned 2-7 days after admission to a drug treatment unit. Eleven age-matched control subjects also were studied. The ISIS localized phosphorus spectra were obtained from a 5-cm thick axial brain slice and a 100-cc white matter volume. In the brain slice, the phosphorus metabolite signal expressed as a percentage of total phosphorus signal was 15% higher for phosphomonoesters, 10% lower for nucleotide triphosphates (beta-NTP), and 7% lower for total nucleotide phosphates in polydrug abusers compared with those in controls. Phosphodiesters, inorganic phosphate, phosphocreatine, total phosphorus, pH, and free magnesium concentration were unchanged. None of these parameters correlated with the methadone dose or the number of days abstinence. Single photon emission computed tomographic imaging of a subgroup of the patients revealed abnormal cerebral perfusion in 80% of the patients scanned. These data suggest that cerebral high energy phosphate and phospholipid metabolite changes result from long term drug abuse and/or withdrawal and that these changes can be detected and studied by 31P MRS.