The objective was to identify pharmacokinetic parameters predictive for tumor response and normal tissue side effects after i.v. administered radiolabeled rabbit antihuman ferritin IgG. Twenty-eight patients with recurrent Hodgkin's disease received 2 mg of rabbit antihuman ferritin i.v., labeled with 4-7 mCi of In-111 followed by two doses of 0.25, one dose of 0.3, or one dose of 0.4 mCi of Y-90-labeled antiferritin per kg of body weight 1 week later. Radioactivity and HPLC measurements of blood and urine samples and liver and tumor volumes identified on sequential whole-body scans provided the data for a pharmacokinetic analysis covering the first 6 days after the administration of the radioimmunoconjugate. Side effects and tumor response were recorded. Temporary hematological toxicity was noted in all patients. Sixteen patients showed a tumor response. The Y-90 blood level at 1 h after administration correlated with the severity of subsequent hematological toxicity. The rapid blood elimination half-life of radioactivity was 4.4 h. Less than 5% of the administered radioactivity was eliminated in the first 24 h urine. The slow blood elimination half-life was 44 and 37 h for In-111 and Y-90, respectively. One of 12 retreated patients produced anti-rabbit IgG antibodies. The volume of distribution was larger for Y-90 than for In-111-labeled antiferritin (160 versus 110% of estimated blood volume). Accidentally extravasated rabbit IgG was rapidly catabolized in perivascular tissues with an effective half-life of less than 35 h. Slower catabolism was noted for rabbit IgG in blood (t(1/2) = 40 h), liver (t(1/2) = 62 h) or tumor (t(1/2) = 40-80 h). Twelve of 13 patients with an effective tumor half-life > 57 h showed a tumor response. I.v. administered polyclonal rabbit antihuman ferritin, labeled with In-111 or Y-90 is stable in vivo and targets Hodgkin's disease. Intravascular Y-90 causes a vascular leak and a larger volume of distribution for antiferritin. Elevated Y-90 blood levels at 1 h and a tumor half-life of >57 h predict for hematological toxicity and tumor response, respectively.