Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations in milk and plasma samples from healthy and mastitic cows were determined by radioimmunoassay and compared with prostaglandins (PGE2, PGF2 alpha and thromboxane B2 [TXB2]), phospholipids and other relevant parameters in milk and blood. The concentrations of cAMP were about five times higher in plasma (p less than 0.01) than in milk, whereas the cGMP concentration in milk was three times higher (p less than 0.01) than that in plasma in both healthy and diseased animals. In mastitic milk, the cAMP and cGMP concentrations were 19% and 65% and in blood plasma 13% and 84% higher respectively than in healthy animals. In milk, cyclic nucleotide concentrations correlated with the markedly elevated cell count and also with the prostaglandin concentration and pH. In blood, cAMP correlated positively with phospholipids and cGMP with reduced glutathione (GSH). These changes are considered to be important in the disease process and, in particular, the increase in cGMP deserves further study.