Morphological changes in parathyroid chief cells were investigated in rats with humoral hypercalcaemia of malignancy (HHM), induced by intraperitoneal inoculation with a rat pulmonary adenocarcinoma cell line, IP-B12. Inoculation with IP-B12 cells resulted in the production of parathyroid hormone-related protein (PTHrP); thus, IP-B12-bearing rats developed hypercalcaemia, with elevated plasma PTHrP concentrations and decreased serum PTH, at 5 to 7 weeks after the inoculation. Morphometrical analysis revealed an increase in the cytoplasmic area of chief cells in IP-B12-bearing rats, as compared with controls. Ultrastructurally, although the number of mature storage granules in the chief cells was similar in controls and IP-B12-bearing animals, degraded granules were significantly increased in tumour-bearing rats. In addition, the chief cells of IP-B12-bearing rats showed a trend towards decreased tortuosity of the cytoplasmic membrane, with simple interdigitations between adjacent cells. These findings suggested that under HHM conditions, PTH granules in the chief cells were maintained in the form of storage granules and were hydrolysed, resulting in the suppression of PTH release into the blood circulation. Serum PTH concentrations may be regulated by inhibition of secretion rather than suppression of granular synthesis in hypercalcaemic rats. This is the first description of morphological changes in the parathyroid gland of rats with HHM.