Over 40 years ago, Grollman reported that unilateral nephrectomy (UN) in rabbits precipitated hypertension and suggested that liberation of a pressor substance by an ischemic or damaged kidney could not be causative. Because others were unable to corroborate that UN in rabbits led to increased blood pressure (BP), we followed 7 rabbits after UN and 4 rabbits after a sham operation. At 7-10 days postoperatively, BP increased from the baseline average of 83 to an average of 97 mm Hg in the UN rabbits (p less than 0.01). In contrast, BP did not change significantly after sham operation. Measurements of blood chemistries, serum insulin levels and digoxin-like substances showed no significant changes after UN which would explain the BP rise, but plasma renin activity (PRA) rose from 11.4 to 30.3 ng/ml/h, (p less than 0.05). However, similar elevations occurred in sham-operated rabbits that showed no significant change in BP, i.e. 10.6-26.2 ng/ml/h. Measurement of serum renotropic activity after UN, but not after sham operation, also showed a significant elevation above baseline 97.6% (p less than 0.001). The renotropic activity 7-10 days after UN unlike PRA correlated significantly with the changes in BP (r = 0.87, p less than 0.001). We conclude that BP rises after UN in rabbits, confirming Grollman's findings. The correlative rise in BP and serum renotropic activity may play an important role in the BP elevation after UN.