Adaptations in adipose tissue lipolysis responsiveness to doses of epinephrine were determined in first lactation Holstein cows. Subcutaneous adipose tissue was biopsied at -30, -15, 30, 60, 120, 180, and 240 d about first calving. Glycerol and fatty acid release from tissue triglycerides were determined in vitro in the presence of 10(-8) to 10(-4) M epinephrine. Basal lipolysis increased postpartum and remained elevated through 240 d of lactation. Glycerol release in response to graded doses of epinephrine increased from 30 d prepartum to 30 d postpartum and remained elevated through 240 d. The highest net response was reached at 120 d and was maintained to 240 d. Increases during lactation were noted in actual glycerol release, net response (stimulated minus basal activity), and maximum net response (calculated from reciprocal plots). Maximal and submaximal response of fatty acid release to epinephrine increased post partum with maximal adaptation occurring by 30 d and remaining elevated through 240 d. Maximum net response of glycerol release at 30 d was related positively (r = .73) to milk energy secretion and negatively to energy intake (r = -.57) and energy balance (r = -.79). Net maximum free fatty acid response at 120 d related positively (r = .89) to milk energy secretion and negatively (r = -.81) to energy balance. The epinephrine responsiveness of adipose tissue increases during lactation in a manner consistent with whole body energy inputs and outputs.