Although best known as a blistering agent, sulfur mustard (HD) can also cause significant neutropenia in exposed individuals, leaving them susceptible to infection. Granulocyte colony stimulating factor (G-CSF) and, more recently, pegylated G-CSF (peg-G-CSF) are approved by the US Food and Drug Administration (FDA) as hematopoietic growth factors used clinically to treat chemotherapy-induced neutropenia. The goal of this study was to determine the effectiveness of recombinant human G-CSF (Neupogen®, Amgen, Inc.) and peg-G-CSF (Neulasta®) in reducing or eliminating HD-induced neutropenia in a non-human primate (NHP) model. A preliminary dose ranging study (3 NHPs each at 0.75, 1.0 or 1.5 mg/kg HD, iv) determined the 1.0 mg/kg, iv, dose to optimally induce neutropenia in African green monkeys (Chlorocebus aethiops). Neutropenia was defined as an absolute neutrophil count (ANC) < 1000 cells/ul. These animals were challenged with 1.0 mg/kg, iv, of HD, and at 1, 3, 5 or 7 days postexposure G-CSF therapy was initiated (10 ug/kg, sc, once/day). Control groups (HD only and G-CSF only) were also included. G-CSF administration continued until the ANC stabilized at or above baseline. Pegylated-G-CSF (peg-G-CSF; 300 ug/kg, sc, single treatment) was similarly tested with treatment given at 3 days postexposure. Neutrophil counts were monitored for 30 days after the initiation of CSF therapy. Untreated HD-exposed NHPs did not recover from neutropenia until day 28 postexposure, whereas the G-CSF- or peg-G-CSF-treated NHPs recovered 8 to 19 days postexposure. These results indicate that G-CSF or peg-C-CSF may provide FDA-approved drugs that will reduce the duration of HD-induced neutropenia. G-CSF or peg-G-CSF treatment could ultimately decrease the duration of antibiotic therapy in patients with secondary infections and reduce the length of patient hospitalization.