BACKGROUND We examined the effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on the subcellular distribution of phospholipids in rat gastric surface mucous cells (SMCs) using the cytochemical stain, iodoplatinate (IP). METHODS The volume of a number of subcellular organelles and the density of IP reactivity within these organelles was determined by modified vertical section stereology. RESULTS The volume occupied by most of the subcellular organelles was not affected by dmPGE2 treatment, with the exception that the volume fraction of two classes of large infranuclear inclusion bodies (LIIB1 and LIIB2, organelles we have previously shown to contain hydrophobic lipids), were significantly expanded by a factor of 3-4-fold. The distribution of IP reactivity among the various subcellular compartments appeared to undergo a shift in response to dmPGE2 treatment. Once again the major prostanoid effect was seen in the infranuclear inclusion bodies, as the volume density of IP reactivity was increased 2-24-fold in LIIB1 and 9-10-fold in LIIB2 in comparison to control values. CONCLUSIONS dmPGE2 administration to rats induces an increase in the volume and IP reactivity of a family of lipid-containing organelles, which may underlie its ability to increase the hydrophobic surface properties of the stomach.