Abstract The inbred mouse strains BALB/cBy (C) and C57BL/6By (B6) differed significantly in their susceptibility to seizures induced by the benzodiazepine inverse agonist methyl β-carboline-3-carboxylate (β-CCM). Following a 5 mg/kg injection of β-CCM, 74% of C (n = 35) and 13% of B6 (n = 40) mice exhibited a convulsion. No sex difference was found. Analysis of the reciprocal F1s failed to show either maternal environmental and/or heterosomal effects. A genetic analysis of the strain difference in susceptibility to β-CCM-induced seizures using recombinant inbred strains (RIS)_was performed. The strain distribution for the RIS showed a two group partition. Statistical analysis showed that, although a one-segregating-unit model could not be rejected to explain the strain difference in β-CCM-induced seizures, some of the evidence weakened the one-segregating-unit hypothesis.