An overview is given of the phenotype of mice with distinct deletions of genes for cytokines and some related proteins, which occur either naturally or as a result of homologous recombination. The use of such knockout mice for investigation of the pathophysiology of experimental disease is summarized. Understanding of the role of a given cytokine in pathogenesis has therapeutic implications, as the pathology may be prevented or attenuated by inhibition of the synthesis, release or activity of that cytokine.