The effect of daily treatment (sometimes interrupted) with the calcium blocker nisoldipine at two different dose levels, one double the other, on the development of spontaneous hypertension in the rat was evaluated. Both doses prevented development of the disorder during daily administration, but when treatment was stopped the same degree of hypertension as in controls quickly developed. Resumption of treatment caused blood pressure to fall to or towards normal again. The higher dose caused a more rapid and greater fall than the lower, and allowed a lesser pressor response when it was discontinued. The drug had no effect on growth, and the only consistent hematological effect was a slight thrombocytosis. Daily treatment at a single dose level slightly reduced normal blood pressure and prevented cortisone hypertension. Serum renin activity was unaffected by nisoldipine but was elevated by cortisone treatment: nisoldipine increased aldosterone levels, but not when cortisone was also given.