To determine whether glucocorticoids would influence the glycosphingolipid composition of the rat kidney, male albino rats of the Sherman strain were subcutaneously administered dexamethasone (100 micrograms/100 g body wt/day) or diluent for four days. The compositions of ceramide and of acidic and neutral glycosphingolipids of the kidneys of these animals were then examined and compared. The results demonstrated that dexamethasone administration: 1) increased the content of ceramide and of acidic and neutral glycosphingolipids in kidney; 2) increased the relative percentage of globotriaosyl- and globotetraosyl-ceramide, but decreased the relative percentages of glucosylceramide; 3) decreased the relative percentages of GM3 and increased other gangliosides; 4) increased the relative percentages of N-glycolylneuraminic acid in GM3; 5) did not appear to influence significantly the long-chain bases of the major glycosphingolipids; and 6) altered the relative percentages and chain length of the hydroxy and nonhydroxy fatty acids of the major acidic and neutral glycosphingolipids in this tissue. The data show that dexamethasone administration induces quantitative and qualitative changes in the glycosphingolipids of the rat kidney.