Phosphorylation of spectrin in whole cells occurs on a single tryptic peptide and indicates a specific and limited modification of spectrin. Phosphorylation of spectrin in soluble extracts and isolated membranes is less specific. Diamide is an inhibitor of erythrocyte spectrin kinase and casein kinase. This agent also inhibits the restoration of biconcave morphology to metabolically depleted erythrocytes reincubated with adenosine.