The neurochemical effect of postnatal exposure to methadone (METH), undernutrition (UND), and methadone and undernutrition (METH-UND) on the whole brain and cerebellum were examined in 21- and 60-day-old rats. At 21 days, body weight reductions of UND and METH-UND rats exceeded that of the METH animals. However, METH rats had the most severe deficits in the weight and total DNA content of the brain and cerebellum, as well as in brain DNA concentration. All experimental rats were subnormal in body weight at 60 days, as was the brain weight of METH-UND rats. Total brain DNA content was most reduced in 60-day-old METH animals, whereas brain RNA content and cerebellar DNA content was only lower in UND and METH-UND animals. These results suggest that methadone often has a greater retarding effect on whole brain and cerebellar development than would be expected by reduced caloric intake alone, and that at least part of the growth inhibiting effects of this drug originates from nonnutritional causes.