The authors examined the pharmacokinetics of the CD 19 receptor‐directed tyrosine kinase inhibitor B43‐Genistein in 17 patients (4 children, 13 adults) with B‐lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5patients with non‐Hodgkin's lymphoma (NHL). The immune conjugate was administered intravenously as a 1‐hour continuous infusion at a dose level of either 0.1 mg/kg (N = 12) or 0.18 mg/kg (N = 5), and the plasma concentration‐time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameters. Pharmacokinetic analyses revealed a plasma half‐life of 19 ± 4 hours, mean residence time of 22 ± 4 hours, and a systemic clearance of 18 ± 2 mL/h/kg. The average (mean ± SEM) values for the maximum plasma concentration Cmax, volume of distribution at steady state (Vss), and area under curve (AUC) were 1092 ± 225ng/ml, 291 ± 37mL/kg, and 9987 ± 2021 μg × h/L, respectively The AUC values were higher at the 0.18 mg/kg dose level than at the 0.1 mg/kg dose level (16,848 ± 5118 μg × h/L vs. 7128 ± 1156 μg × h/L, p = 0.009). Patients with ALL had a significantly larger volume of distribution at steady state (332 ± 47 mL/kg vs. 191 ± 12 mL/kg, p = 0.04), faster clearance (21 ± 3 mL/h/kg vs. 11 ± 2 mL/h/kg, p = 0.03), and lower dose‐corrected AUC than patients with NHL (6010 ± 836 μg × h/L vs. 12,044 ± 2707 μg × h/L, p = 0.006). There was a trend toward faster clearance rates (23 ± 4 mL/h/kg vs. 16 ± 3 mL/h/kg, p = 0.1), shorter elimination half‐lives (5.7 ± 3.6 hours vs. 13 ± 8.8 hours, p = 0.1), and shorter mean residence times (11 ± 3 hours vs. 25 ± 5 hours, p = 0.08) for non‐Caucasian patients as compared to Caucasian patients. When compared to adult patients, pediatric patients showed a significantly larger volume of distribution at steady state (418 ± 82 mL/kg vs. 252 ± 34 mL/kg, p = 0.02) and a longer elimination half‐lives (18.4 ± 13.6 hours vs. 8.7 ± 6.7 hours, p = 0.04). The pharmacokinetics of B43‐Genistein was not affected by the gender of the patients or by bone marrow transplantation in past medical history. Overall, B43‐Genistein showed favorable pharmacokinetics in this heavily pretreated leukemia/lymphoma patient population, which is reminiscent of its recently reported favorable pharmacokinetics in cynomolgus monkeys. To our knowledge, this is the first clinical pharmacokinetics study of a tyrosine kinase inhibitor containing immunoconjugate.