SUMMARYThe standard mixed lymphocyte culture assay, which measures the incorporation of [3H]thymidine into DNA, usually requires 5 days. We describe a more rapid assay based on changes in the activity of ornithine decarboxylase. An increase in the activity of ornithine decarboxylase was observed in mixed lymphocyte cultures from genetically defined, major histocompatibility complex (MHC)-nonidentical miniature swine as early as 18 hr after plating. No increase was found in mixed cultures from inbred MHC-identical animals. Similar results were obtained with the enzyme S-adenosylmethionine decarboxylase with the increase in activity starting at about 32 hr. There was a good correlation between the ornithine decarboxylase values at 18 hr and the results of the [3H]thymidine incorporation assay on day 5. Preliminary experiments with human lymphocytes revealed similar results.