Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.