An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration. The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used. Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments. Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate. No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis. Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml. Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients. After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients. These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis. Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary.