1. Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and cyclic guanosine 3', 5'-monophosphate (cyclic GMP) have been estimated in the kidneys of rats.2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.4. When an anephric rat was cross-circulated with a normal litter-mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.5. In experiments where one kidney of a litter-mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys.