The influence of sex and age on the expression pattern of preprotachykinin-A (PPT-A) mRNA isoforms encoding substance P and other tackykinins such as neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide gamma (NPgamma) in human immunocompetent cells and the role of this pattern on SP production are unknown. To investigate these questions, we assessed PPT-A isoform expression and SP production in CD3+ lymphocytes of normal healthy subjects. There were no significant differences in PPT-A isoforms in relation to sex or age. The most frequently expressed isoforms were beta and gamma: after lymphocyte stimulation with phytohemagglutinin (PHA), there was a significant increase in their frequency (p<0.0001). Significantly higher SP levels were found in subjects expressing beta and gamma PPT-A than in those with beta PPT-A only (p=0.001). These findings provide evidence of a heterogeneous expression of PPT-A isoforms in CD3+ lymphocytes of normal healthy subjects.