Clinical states of hyperglucocorticoidism are associated with renal metabolic alkalosis, yet the systemic and renal acid-base response to chronic administration of glucocorticoid steroids (dexamethasone, triamcinolone) possessing little or no mineralocorticoid activity has not been investigated. In balance studies studies in dogs administration of triamcinolone (Tcn), 1.0 mg . kg-1 . day-1 for 6-9 days (group I, n = 5), resulted in a persistent reduction in urine pH and increase in net acid excretion (NAE), and in the excretion of urinary unmeasured anions (C+NH4,Na;K minus A-Cl,HCO3,Pi), which were identified as organic anions and sulfate. A significant degree of metabolic acidosis occurred initially (delta [HCO3-]p, -3.4 meq/liter, P less than 0.05, day 1). As Tcn administration was continued, the cumulative increment in net acid excreted exceeded the cumulative increment in urinary unmeasured anion excreted and [HCO-3]p returned to pre-Tcn control values and remained stable thereafter. In the steady state of Tcn administration plasma potassium concentration and renal potassium clearance were not significantly different from pre-Tcn control, in contrast to the findings of hypokalemia and increased renal potassium clearance during chronic administration of deoxycorticosterone (DOC). Triamcinolone did not result in antinatriuresis or antichloruresis. Chronic administration of a 10-fold smaller dose of Tcn (0.1 mg . kg-1 . day-1) in an additional group (group III) also resulted in a persisting reduction in urine pH and an increase in net acid excretion that exceeded unmeasured anion excretion and resulted in a small increase in steady-state plasma bicarbonate concentration. These results suggest that chronic administration of potent glucocorticoid steroids results in 1) a persisting increase in endogenous acid production, and 2) stimulation of renal hydrogen ion secretion that was of greater degree than accounted for by the increment in endogenous acid production and that was not accompanied by renal mineralocorticoid effects on sodium and potassium transport.