The primary dose-limiting adverse effects associated with foscarnet treatment of cytomegalovirus retinitis in patients with AIDS are renal impairment and ionized hypocalcemia. Dose-limiting renal impairment, consisting of significant alterations in serum creatinine levels or creatinine clearance or acute renal failure, has been observed in 10-20% of AIDS patients receiving foscarnet via intermittent i.v. infusion. Nephrotoxicity can be minimized by adjusting dosage according to creatinine clearance and by ensuring that adequate hydration is provided throughout foscarnet therapy. Transient decreases in serum or plasma ionized calcium levels appear to occur in all patients during foscarnet infusion, with these decreases being observed in the absence of changes in total calcium levels. Hypocalcemia produces mild symptoms in some patients and may play a role in unexplained cases of arrhythmia or seizure. Careful attention should be given to levels of total calcium and other minerals during foscarnet treatment, and the occurrence of symptomatic hypocalcemia should prompt evaluation of ionized calcium concentrations and foscarnet dose reduction. Another potentially treatment-limiting effect attributed to foscarnet is penile ulceration, which appears to result from exposure of the glans penis to unchanged foscarnet in the urine.