The role of sympathetic nerves in the control of brown adipose tissue (BAT) growth was studied by quantitative photonic autoradiography using [3H]-thymidine to follow mitotic activity. The effects of cold exposure (4 days at 5 degrees C) and chronic norepinephrine treatment (0.375 mumol/h for 4 days at 25 degrees C) were compared in intact and denervated interscapular BAT pads of adult rats. The denervated pads were paler than the contralateral innervated sides and contained numerous adipocytes filled with large lipid droplets. In the innervated BAT pad, cold exposure markedly enhanced the labeling frequency in brown adipocyte precursor cells (interstitial cells and preadipocytes) and in endothelial cells forming the numerous blood capillaries (P < 0.01). However, in the denervated BAT pads, the effects of cold exposure on cell proliferation were markedly inhibited. Remarkably, norepinephrine infusion at 25 degrees C mimicked the effects of cold exposure on the coordinated proliferation of the different cellular types, both in the innervated and denervated pads. These results demonstrate that intact sympathetic nerves are required for the stimulation of mitotic activity in BAT by cold exposure but not by norepinephrine infusion. It appears therefore that norepinephrine release from sympathetic nerves represents the initial stimulus in a chain of metabolic events leading to BAT hyperplasia. However, sympathetic or sensory nerves may still contain factors modulating cell proliferation and differentiation in BAT.