When pancreastic elastase is introduced into the lungs of hamsters to produce emphysema, there is an initial rapid destruction of elastin followed by a subsequent resynthesis. In order to investigate its pathologic significance, we attempted to interfere with this resynthesis by feeding inhibitors of elastin cross-linking. The feeding of the lathyrogens beta-aminoproprionitrile (beta APN) or penicillamine resulted in a marked worsening of the elastase-induced emphysema, as measured by the average distance between alveolar walls and the internal alveolar surface area, when compared with the effect of elastase in animals fed a normal diet. The lathyrogens produced no effect on lung morphology without elastase injections. In elastase-injected animals, the principlal biochemical effect of beta APN was a decrease in the aldehyde content of the elastin without a measurable decrease in desmosine cross-links. These results indicated that the formation of normal connective tissue proteins during the replair of elastolytic injury helps to limit the degree of anatomic deformity that is produced.