The effect of hydrocortisone (HC) (200 mg, i.v. over 15 min) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg sc), and on basal prolactin (PRL) secretion was studied in 11 normal male volunteers. In addition, the effect of HC on 3H-spiperone binding to rat striatal membranes was investigated. HC alone increased basal GH secretion compared with placebo (p less than 0.02) commencing 90 min after injection (p less than 0.05). When HC was given before Apo the GH response to Apo was blunted (p less than 0.05), and the delayed HC-induced increase was absent (p less than 0.001). HC or Apo alone had no effect on PRL secretion but HC plus Apo significantly decreased PRL concentrations compared with placebo (p less than 0.01) or HC alone (p less than 0.001). HC (0.1-100 microM) had no effect on 3H-spiperone binding in vitro. The mechanisms involved in the effect of HC on GH and PRL are unclear. The ability of HC to both stimulate and antagonize GH secretion points to multiple sites of action within the hypothalamic-pituitary axis.