The potential role of the kidney in renal serine synthesis was elucidated in rats following dietary serine as well as serine and glycine depletion for 6 weeks. Serine deficient diet caused a significant rise in blood serine and glycine values. In contrast, blood glycine concentration decreased significantly following serine and glycine depletion, whereas blood serine levels remained unchanged. Bilateral nephrectomy caused a significant decrease of blood serine values of control and serine deficient rats. Serine concentration, however, was not affected by bilateral nephrectomy following serine and glycine deficiency indicating kidney-independent serine synthesis under these conditions. There was a significant increase of blood lactate and pyruvate levels under serine and serine/glycine deficient diet compared with control animals, whereas blood ketone bodies fell. In contrast, 24 h after bilateral nephrectomy blood ketone bodies rose and blood lactate and pyruvate concentrations decreased significantly. 24 h after bilateral nephrectomy there was a marked rise in blood citrate values of female rats compared with male animals indicating sex dependency of kidney citrate metabolism in the rat.