Congenital recessive ichthyosis has a broad range of clinical presentations, which may be considered a spectrum of phenotypes with classic lamellar ichthyosis at one pole and classic congenital ichthyosiform erythroderma at the other. The identification of mutations in the transglutaminase-1 gene as a cause of lamellar ichthyosis implicates transglutaminases in other congenital recessive ichthyoses. We investigated two multiplex families with clinical manifestations between the two poles for linkage to the transglutaminase-1 locus on chromosome 14. Strongly negative lod scores prompted a search for linkage to two other epidermally expressed transglutaminases, transglutaminase-2 and transglutaminase-3, on chromosome 20. No evidence for linkage was found. These data confirm the hypothesis that the congenital recessive ichthyoses are genetically heterogeneous and in two families exclude two other transglutaminases that could be considered as candidate loci for at least some of the nonlamellar recessive ichthyoses.