1 In the present study, for the ®rst time, PDE4 subtypes were identi®ed and semi-quanti®ed in both CD4 and CD8 lymphocytes from healthy and asthmatic individuals. 2 CD4 and CD8 lymphocytes from healthy and mild asymptomatic asthmatic subjects (receiving bagonist therapy only) were isolated from peripheral venous blood using appropriate antibody coated paramagnetic beads. PDE4 subtypes and b-actin were identi®ed by digoxigenin (DIG)-labelling reverse transcriptase-polymerase chain reaction and semi-quanti®ed by DIG-detection enzyme-linked immunosorbance assay. 3 In CD4 and CD8 lymphocytes PDE4A, PDE4B and PDE4D were detected, with no signi®cant di erences observed between healthy and asthmatic groups. In CD8 lymphocytes, enzyme subtype expression was lower and showed more intersubject variability. 4 In functional studies investigating the e ects of various PDE inhibitors on PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects, CDP840 (0.03 ± 10 mM), rolipram (0.1 ± 10 mM) and theophylline (10 mM ± 1 mM) inhibited PHA-induced proliferation of mononuclear cells from healthy and asthmatic subjects in a concentration-dependent manner, although no signi®cant di erence was observed between the groups investigated. 5 In additional studies, total monocyte cyclic AMP PDE activity was investigated in cells isolated from asthmatic subjects both prior to and 24 h after allergen challenge. Total monocyte cyclic AMP PDE activity remained una ected following challenge of asthmatic subjects with either house dust mite or cat dander and was inhibited in a concentration-dependent manner by rolipram (0.01 ± 100 mM) both before and after allergen challenge.