Nifedipine has been shown to lower urinary calcium in essential hypercalciuria. However, the mechanism(s) by which this action takes place is completely unknown. This study describes the effect of nifedipine on some calcium-controlling hormones in essential hypercalciuria. Nifedipine (20 mg/day) was administered to ten essential hypercalciuric patients, and urinary PgE₂, plasma bicyclic PgE₂, 1,25 vitamin D₃, and PTH were assayed before and after drug administration. Nifedipine promoted a significant fall in urinary calcium (352.1±87.67 SD vs. 231.2±74.62 mg/24 hr; t=7.35, p<.0001) and PgE₂ (343.92±42.71 vs. 245.03±35.41 SD ng/24 hr; t=6.18, p<.0002), as well as in plasma bicyclic PgE₂ (310.00±30.91 vs. 200.00±31.62 SD pg/ml; t=9.86, p<.0001) and 1,25 (OH)₂ vitamin D₃ (32.77±3.23 vs. 26.94±2.94 SD pg/ml; t=6.53, p<.0001), while PTH remained unaltered (18.50±3.63 vs. 19.50±4.09 SD ng/ml; t=0.85, p, ns). Urinary calcium and PgE₂ correlated positively before (r=0.81, p<.005) but not after treatment. The fall in urinary PgE₂ brought about by nifedipine seems to be due to an inhibition of PgE₂ synthesis, since the absolute decrements in both urinary PgE₂ and plasma PgE₂ metabolites were positively correlated (r=0.79, p<.007). No correlation was found between the absolute decrements of plasma bicyclic PgE₂ and 1,25 (OH)₂ vitamin D₃.