Bone marrow transplantation (BMT) in mice was utilized to determine the relative importance of carbonic anhydrase II (CA II) deficiency in blood compared to kidney in the pathogenesis of the ammonium chloride intolerance observed in CA II-deficient mice. "Normal" BMT experiments utilized normal donors and CA II-deficient recipients (NL-->DEF), "reverse" BMT experiments utilized CA II-deficient donors and normal recipients, and control BMT experiments utilized normal mice with a hemoglobin polymorphism (Hbb d/s). Unstressed urinary pH was not significantly altered by normal or reverse BMT, nor was any change induced by control BMT. However, DEF-->NL mice showed markedly altered weight changes when placed on oral ammonium chloride, an effect apparently secondary to dehydration due to decreased water intake. In addition, some CA II-deficient mice have a urinary concentrating defect. Red blood cell and kidney CA II deficiency contribute additively to these effects.