In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with intravenous pamidronate were investigated. A total of 80 patients with proven malignancy and pain due to osteolytic bone disease were enrolled. Doses of 30 mg, 45 mg, 60 mg and 90 mg pamidronate, given every 4 weeks, 3 weeks or 2 weeks were tested. Thus dose intensity was increased by giving higher doses and/or by shortening the intervals. A combined palliation score on the bases of pain score (WHO), analgesic score (WHO) and improvement of performance status (SAKK/ECOG) was rated by the physician on a six-point scale. Regression analysis showed a close correlation between dose intensity and effect (Pearson's R = 0.7: P < 0.0001). A statistically significantly different palliative score for patients treated with low (below 15 mg/week), medium (16-30 mg/week) and high doses (above 31 mg/week) of pamidronate was found (P= < 0.01). A dose intensity below 10 mg pamidronate/ week and single doses of 30 mg had no clinically relevant benefit, whereas dose intensities of 25-45 mg/week showed a significant palliative effect. We conclude that pamidronate should be given in a close intensity of 20 mg per week or more in patients with far advanced osteolytic bone disease. Best results are obtained with high doses of 60 mg or 90 mg pamidronate. Further investigations by prospective randomized trials are needed to determine the optimal dose and schedule of pamidronate infusions.