Treatment of neonatal mice with large, repeated doses of monosodium L-glutamate (MSG) produces a syndrome of obesity and endocrinological dysfunction generally attributed to a hypothalamic lesion. We have used single injections of MSG, administered on postnatal day four, to explore the lower end of the dose-response curve for this toxin. Major features of the MSG syndrome including hypophagia, obesity, hypoactivity, reduced pituitary protein content, decreased ovarian weight, delayed puberty and elevated plasma corticosterone levels were obtained at the highest dose. Of the variables measured, feeding disturbances and reduced pituitary and ovarian weights were the most sensitive indicators of damage. The extent of damage produced in the arcuate nucleus of the hypothalamus increased with increasing dose. A prominent lesion was also detected in the medial preoptic area of animals receiving the highest dose. Damage was not evident in other diencephalic structures associated with body weight regulation. Since little is known about the mechanisms underlying MSG obesity, a second study examined the contribution of ovarian hormones to obesity in MSG treated mice. Ovariectomy increased the body weights of animals injected with low but not high doses of MSG, suggesting that a reduction in ovarian function may contribute to the MSG obesity syndrome in the female. Measurement of hypothalamic monoamines and metabolites in these mice indicated that as with repeated doses of MSG, single injections of the toxin reduced hypothalamic dopamine levels. DOPAC levels were unchanged.