The effects of sodium pump inhibitors of the cardiac glycoside family (strophanthin K and digoxin) on neurite growth in the sensory ganglia of chick embryos (10-12 days) were studied in organotypic tissue cultures. These experiments produced the first evidence that these medicinal agents have marked neurite-suppressing actions. Their effects on sensory ganglion neurite growth were dose-dependent. At 1.10(-6) M, strophanthin K and digoxin completely blocked sensory ganglion neurite growth. Addition of study compounds to the medium at a concentration of 1.10(-7) M decreased the area index of the experimental explants to a level significantly below that of the controls, by a mean of 45%. These strophanthin K and digoxin concentrations were comparable with those at which endogenous digitalis-like factors are present in the systemic circulation. These results provide evidence that cardiac glycosides can produce the directed regulation of nervous tissue growth by affecting the signal transducer Na+, K+-ATPase.