The aim of the study was to evaluate the polymorphonuclear leukocyte (PMN) membrane fluidity and PMN cytosolic Ca
$^{2+}$
content in several clinical conditions: diabetes mellitus, vascular atherosclerotic disease (VAD), chronic renal failure (CRF), essential hypertension (EH). In 13 subjects with insulin‐dependent diabetes mellitus (IDDM), in 24 subjects with non‐insulin‐dependent diabetes mellitus (NIDDM), in 42 VAD subjects, in 23 VAD subjects with NIDDM, in 15 subjects with CRF and in 12 subjects with EH, we determined the PMN membrane fluidity, obtained marking unstimulated PMN cells with fluorescent probe 1‐[4‐(trimethylamino)phenyl]‐6‐phenyl‐1,3,5‐hexatriene (TMA‐DPH), and considering the fluorescence polarization degree, and the PMN cytosolic Ca
$^{2+}$
content, obtained marking unstimulated PMN cells with the fluorescent probe Fura2‐AM and considering the ratio between the Fura2‐Ca
$^{2+}$
complex and the unchelated Fura2 fluorescence intensity. From the obtained data it is evident that PMN membrane fluidity does not distinguish normals from IDDM subjects, NIDDM subjects, VAD subjects with and without NIDDM, CRF subjects and hypertensives. PMN cytosolic Ca
$^{2+}$
content, in comparison with normal controls, is significantly increased in VAD subjects (
$p<0.01$
), in VAD subjects with NIDDM (
$p<0.001$
), in CRF subjects (
$p<0.001$
) and in hypertensives (
$p<0.05$
). No correlation was found between PMN membrane fluidity and PMN cytosolic Ca
$^{2+}$
content. The study of these PMN parameters can be useful in the understanding of the role of leukocytes in the vascular damage that characterizes these clinical conditions.