The aim of this study was to determine the maximum tolerated dose of ⁹⁰Y-DOTATOC per cycle administered in association with amino acid solution as kidney protection in patients with somatostatin receptor-positive tumours. Forty patients in eight groups received two cycles of ⁹⁰Y-DOTATOC, with activity increased by 0.37 GBq per group, starting at 2.96 and terminating at 5.55 GBq. All patients received lysine ± arginine infusion immediately before and after therapy. Forty-eight percent developed acute grade I–II gastrointestinal toxicity (nausea and vomiting) after amino acid infusion whereas no acute adverse reactions occurred after ⁹⁰Y-DOTATOC injection up to 5.55 GBq/cycle. Grade III haematological toxicity occurred in three of seven (43%) patients receiving 5.18 GBq, which was defined as the maximum tolerable activity per cycle. Objective therapeutic responses occurred. Five GBq per cycle is the recommended dosage of ⁹⁰Y-DOTATOC when amino acids are given to protect the kidneys. Although no patients developed acute kidney toxicity, delayed kidney toxicity remains a major concern, limiting the cumulative dose to ~25 Gy. The way forward with this treatment would seem to be to identify more effective renal protective agents, in order to be able to increase the cumulative injectable activity and hence tumour dose.