A phase I study was performed to determine the safety and tolerability of injecting autologous CD34⁺ cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34⁺ cell population in granulocyte colony‐stimulating factor (G‐CSF)‐mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34⁺ stem cell population from the majority of the CD34⁺ cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34⁺ cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription‐polymerase chain reaction‐based gene expression analysis indicated that the adherent CD34⁺ cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34⁺ cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34⁺ cell population contains cells with the potential to form hepatocyte‐like cells, we gave G‐CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 × 10⁶ and 2 × 10⁸ CD34⁺ cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.