We present a modified (non-segmental) method for quantification of regional left ventricular dysfunction using gated myocardial perfusion SPET. Gated SPET is increasingly used to obtain complementary information on local perfusion and to assess the relevance of deficits in segmental count densities (attenuation vs perfusion deficit). The non-segmental approach was motivated by a hypothetical limitation regarding the validity of commonly used methods of quantitative wall thickening (WT) analysis. These methods are all based on segmental analysis, which could cause underestimation of 'true' contractile dysfunction in perfusion defects that do not have a strict segmental distribution. SPET images gated in eight time bins 60 min after the injection of 740 MBq 99Tcm-tetrofosmin or 99Tcm-sestamibi were recorded on a triple-headed camera in 20 normal subjects and in 16 patients within 2 weeks and again 3 months after myocardial infarction. Normal limits of wall thickening, calculated from pooled wall thickening profiles obtained in normal subjects, were used to identify and quantify areas with abnormal wall thickening in patients with coronary artery disease. The method was validated against data obtained from contrast ventriculography (CVG) and tested for reproducibility. The reproducibility of the method was excellent: r = 0.98 (WTsev measure 1 = 1.03WTsev measure 2 - 0.01). The localization of wall thickening abnormalities detected by gated SPET correlated well with the localization of regions with abnormal wall motion (WM) identified by CVG. The severity of the regional myocardial dysfunction assessed by gated SPET was closely correlated with the severity of the regional myocardial dysfunction derived from CVG: r = 0.85 (WMsev = 2.55WTsev + 2.30). Furthermore, a good correlation between the total wall thickening severity score and the global left ventricular ejection fraction (LVEF) was observed early and late after myocardial infarction: r = 0.80 (WTsev = -0.4LVEF + 0.46). We conclude that quantitative analysis of regional wall thickening assessed from gated SPET myocardial perfusion scintigraphy is a reliable parameter for regional ventricular function. Categorizing wall thickening abnormalities quantitatively may be helpful in assessing small changes in regional function that may occur between sequential gated SPET images.