We have generated mouse null mutants for the cellular retinoic acid (RA) binding protein type I (CRABPI), a protein whose spatio-temporal expression pattern coincides with the target tissues for RA action. Inactivation of the CRABPI gene was accomplished via homologous recombination in embryonic stem cells. Cells carrying the correctly targeted gene were injected into blastocysts and the resulting chimaeras yielded offspring heterozygous for the knockout mutation. Subsequent breeding programs resulted in normal litter sizes containing viable and fertile CRABPI deficient mice. Homozygous mice carrying the knockout mutation were studied in detail to detect possible organ and skeletal anomalies and/or abnormalities of the hematopoietic system. No overt phenotype was evident indicating that a deficiency for CRABPI does not seem to interfere with normal development, growth and reproduction.