The galactopoietic actions of bovine somatotropin are both direct and indirect. Indirect actions are apparently mediated by the insulin-like growth factor (IGF) system. The objective of this study was to compare systemic (plasma) versus local (lymph) concentrations of IGF. Afferent mammary lymph most nearly represents the extracellular fluid that is bathing mammary tissue. Catheters were surgically implanted in the jugular vein and the superficial afferent mammary lymph vessels of four lactating cows. A crossover design was utilized to evaluate the effects of bovine somatotropin (bST). After 2 d of basal sampling, either bST (40 mg/d) or excipient was administered daily for 5 d. After the conclusion of the bST study, a second study was conducted in which cows were deprived of feed for 36 h. Blood and lymph were simultaneously sampled at least every 6 h throughout both studies. Milk yield was increased by bST, and concentrations of IGF-I were increased in plasma and lymph. The relationship between plasma and lymph concentrations for IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids were similar during bST treatment. Milk yield was reduced 76% by 36 h of feed deprivation. Feed deprivation also caused a reduction of IGF-I in plasma, but concentrations of IGF-I in lymph were not altered. In contrast, changes in IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids that were caused by feed deprivation followed similar patterns in plasma and lymph. Clearly, if IGF-I mediates the mammary actions of bST, then concentrations of IGF-I in plasma correlate with milk yield responses as well as, if not better than, concentrations in lymph.