Following the development of methods for eliciting and purifying digoxin-specific Fab fragments with high affinity and specificity for cardiac glycosides, clinical studies were undertaken as a multicenter, open-label trial to test safety and efficacy in patients with advanced and potentially life-threatening digitalis toxicity that failed to respond to conventional therapeutic measures. One-hundred fifty such patients were treated with digoxin-specific antibody fragments purified from immunoglobulin G (IgG) produced in sheep. Doses of Fab were equivalent to the amount of digoxin or digitoxin in the patient's body, as estimated from the medical history or serum concentration measurements. Of 150 patients included in this trial, detailed information is available on 148. One-hundred nineteen (80%) had resolution of all signs and symptoms of digitalis toxicity following specific Fab fragment infusions, 14 (10%) improved, and 15 (10%) showed no response. Among 14 patients with adverse events possibly or probably caused by Fab, the most common events were development of hypokalemia and exacerbation of congestive heart failure. Analysis of the available clinical data indicates that a treatment response was observed in at least 90% of patients with convincing evidence of advanced and potentially life-threatening digitalis toxicity. The data from this multicenter trial have been augmented by findings from an observational surveillance study conducted to monitor the safety and effectiveness of treatment with digoxin immune Fab (ovine) following commercial availability. In this experience, 74% of patients were judged to have a complete or partial response to treatment, and 12% no response. The response for the remaining 14% was not reported or reported as uncertain. In this clinical experience, digoxin-specific Fab was generally well tolerated and clinically effective in patients with potentially life-threatening digitalis toxicity.