Murine G-alpha-14 and G-alpha-15 cDNAs encode distinct alpha-subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins). These alpha-subunits are related to members of the G(q) class and share certain sequence characteristics with G-alpha(q), G-alpha-11, and G-alpha-16, such as the absence of a pertussis toxin ADP-ribosylation site. G-alpha-11 and G-alpha(q) are ubiquitously expressed among murine tissues but G-alpha-14 is predominantly expressed in spleen, lung, kidney, and testis whereas G-alpha-15 is primarily restricted to hematopoietic lineages. Among hematopoietic cell lines, G-alpha-11 mRNA is found in all cell lines tested, G-alpha(q) is expressed widely but is not found in most T-cell lines, G-alpha-15 is predominantly expressed in myeloid and B-cell lineages, and G-alpha-14 is expressed in bone marrow adherent (stromal) cells, certain early myeloid cells, and progenitor B cells. Polyclonal antisera produced from synthetic peptides that correspond to two regions of G-alpha-15 react with a protein of 42 kDa expressed in B-cell membranes and in Escherichia coli transformed with G-alpha-15 cDNA. The expression patterns that were observed in mouse tissues and cell lines indicate that each of the alpha-subunits in the G(q) class may be involved in pertussis toxin-insensitive signal-transduction pathways that are fundamental to hematopoietic cell differentiation and function.