Twenty-four barrows were divided among eight treatments in a 2 x 2 x 2 design to quantify the influence of ractopamine (0 or 20 mg/kg diet) over the final 40 kg of gain on metabolic activity in adipose tissue. Interactions with genotype (Hampshire cross or Landrace cross) and slaughter weight (100 or 127 kg) were investigated also. Backfat was removed at slaughter and rates of lipolysis and fatty acid synthesis (FS), activities of malic enzyme (ME) and fatty acid synthetase (FAS), and insulin binding to adipocytes were assessed. Adipocytes from ractopamine-fed pigs were less sensitive (EC50 increased 90%) and had a lower maximum lipolytic response (40%) to ractopamine stimulation. Rates of basal and insulin-stimulated FS were decreased 40% in ractopamine-fed pigs and were reflected in lower activities of ME (50%) and FAS (15%). Breed and slaughter weight had no consistent influence on the ractopamine response. Landrace-cross pigs had greater insulin binding capacity (30-60%) whether data were expressed on a cell or surface area basis. Ractopamine feeding did not consistently affect insulin binding capacity. Results suggest that ractopamine interacts in vivo with the beta-adrenergic receptor of swine adipocytes, decreasing lipogenic capacity and diminishing responsiveness to beta-adrenergic stimulation.