Adenylate cyclase activity in a tubular fraction obtained from rabbit renal cortex was stimulated by typical adenosine receptor agonists with a rank order of potency NECA (5'-(N-ethyl-carboxamido)-adenosine) (EC50 = 0.48 mumol/l) greater than R-PIA [(-)N6 (R-phenylisopropyl)-adenosine] (3.22 mumol/l). The stimulatory effect of NECA was competitively antagonized by 8-phenyltheophylline. Contamination of the tubular fraction with glomeruli and microvessels was less than 2%, as verified by tissue renin determination and could, therefore, be ruled out as being responsible for the observed effect. Tubular A2-adenosine receptors are probably involved in the control of renal electrolyte secretion and may represent the site of action of methylxanthines.