The phosphoinositide 3-kinase (PI3K) catalytic subunit p110delta, the most recently discovered member of the heterodimeric Class IA PI3K family, has been detected uniquely in leukocytes, but not in one member of the leukocyte family: platelets. We have examined freshly prepared isolates of human platelets for the presence of this enzyme, realizing that p110delta is highly susceptible to proteolytic degradation. We have utilized p110delta-directed Western blotting, RT-PCR, PI3K activity assays, and immunoprecipitations of PI3K Class IA subunits p85alpha, p85beta, and p110delta from lysed human platelets, as well as Triton X-100-insoluble cytoskeletal preparations from resting and thrombin receptor-activated platelets. We report that p110delta is present in association with p85alpha and p85beta in platelets, both in cytosolic and cytoskeletal fractions. The latter finding is consistent with the proposed role of p110delta in cytoskeletal function. (C) 2002 Elsevier Science (USA). All rights reserved.