The effects of pertussis toxin (PT) on cyclic adenosine monophosphate (cAMP) metabolism in lung and spleen tissue of mice were studied. We observed a marked lymphocyte accumulation and concomitant weight increase in the lungs of mice treated with PT. On the contrary, a rapid lymphocyte depletion was observed in the spleens of PT-treated mice. The effects of PT on cAMP metabolism were partially evident in the lungs where early increased levels of cAMP were observed. On the other hand, decreased levels of cAMP in spleen tissues were observed at the time of maximum lymphocyte depletion of such organ.