Glutathione S-transferase (GST) enzymes protect cells against xenobiotics and oxidative stress products through an electrophilic conjugation process. We investigated the theta (GSTT1) and mu (GSTM1) null genotypes in a group of leukopenic subjects and normal subjects from Northeast Brazil, evaluating their use as biomarkers of susceptibility for developing leukopenia. In a sample-based case–control study, we analysed white blood cell (WBC) counts and GSTT1 and GSTM1 genotypes. A total of 278 subjects were analysed: 91 with leukopenia and 187 controls. GSTT1 null genotype conferred a 5.92-fold risk for occurrence of leukopenia [odds ratios (OR) = 5.92, CIMLE: 1.64–26.72, PMLE = 0.002] and a 3.90-fold risk of neutropenia (OR = 3.90; CIMLE: 1.05–13.66; PMLE = 0.02), while GSTM1 null genotype conferred a 1.78-fold risk for leukopenia (OR = 1.75; CIMLE: 1.04–3.06, PMLE = 0.017) and no risk of neutropenia (OR = 1.71; CIMLE: 0.88– 3.35; PMLE = 0.06). The GSTT1, but not the GSTM1 null genotype, was found to be associated with leukopenia and neutropenia. More cellular and molecular studies are needed to evaluate the existence of genotype interactions, and to confirm the appropriateness of using the GSTT1 and/or GSTM1 null genotypes as biomarkers of susceptibility to white blood-cell deficiencies.