Although a number of investigators have examined the uptake of chromium in red blood cells (RBC) or whole blood, little is known about chromium uptake in white blood cells (WBC). Radiolabeled chromium (51Cr) was used to determine chromium uptake and distribution. Isolated RBC and enriched WBC populations were exposed in vitro to potassium chromate (Cr+6) and uptake was determined over a 2-hr time period. Exposure of either rat or human blood cells to 50 μm K2CrO4 for 2 hr resulted in greater accumulation of chromium within WBC than RBC. Uptake by rat WBC was significantly greater than that of human; whereas, uptake by human RBC was greater than that of the rat. Exposure of human whole blood to 50 μm K2CrO4, prior to isolation of WBC, also resulted in an increased uptake of chromium by WBC. Fisher 344 rats were exposed either orally or intravenously to a single dose of K2CrO4 and the distribution of chromium within blood cells was determined 1 hr, 24 hr, or 7 days following exposure. Regardless of the route or time following exposure, WBC chromium levels were consistently greater than those of RBC. However, the absolute levels of chromium did change with time. A comparison of chromium distribution 24 hr following a single oral exposure (1 ppm Cr+6) to the distribution 7 days following exposure demonstrated a reduction in chromium levels for RBC (10-fold) and for WBC (∼2.5-fold). In contrast, intravenous administration of chromate resulted in no significant decrease in RBC chromium levels when compared 1 hr, 24 hr, and 7 days following exposure. Although no difference in WBC chromium content was observed at 1 and 24 hr after exposure, an approximate 1.7-fold decrease in chromium content was detected at Day 7 for WBC. Intravenous administration of chromic chloride (Cr+3) resulted in a low level of chromium associated with RBC following 1 hr, and chromium was undetected in the WBC. These data demonstrate that WBC accumulate hexavalent chromium following both in vitro and in vivo exposure. In addition, white blood cells accumulate chromium to a greater extent than red blood cells. Since WBC accumulate chromium, their use as a target for the development of biomarkers of chromium exposure may be warranted. © 1991.