The effect of aluminum on parathyroid hormone secretion was examined using collagenase-dispersed bovine parathyroid cells. An increase in the medium aluminum concentration over the range of 0.5 to 2.0 mM, in low calcium medium, progressively inhibited the secretion of radioimmunoassayable hormone. At 2.0 mM aluminum hormone secretion was inhibited by 68% while high medium calcium, without aluminum, maximally inhibited parathyroid hormone secretion only 39%. Individually, 2.0 mM aluminum or 2.0 mM calcium inhibited isoproterenol-stimulated hormone secretion by 43%. Either metal suppressed basal and isoproterenol-stimulated cyclic AMP levels of the parathyroid cells. That the inhibitory effect of aluminum on parathyroid hormone secretion was not due to an irreversible toxic effect was demonstrated by a restoration of normal secretion when cells were returned to 0.5 mM calcium medium without aluminum. The incorporation of [3H]leucine into total cell protein, parathyroid secretory protein, proparathyroid hormone, or parathyroid hormone was not affected by aluminum. The secretion of radiolabeled protein was, however, inhibited by aluminum. These results suggest that aluminum does not affect protein biosynthesis of the parathyroid cell or the conversion of proparathyroid hormone to parathyroid hormone. Aluminum appears to directly affect the secretion of protein from dispersed parathyroid cells.