Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamine D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determne whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR interstinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins. CaBP(9K) and CaBP(28K) were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 ± 0.002 vs. 0.186 ± 0.002 IE/min·μm3 x 103 brush border, mean ± SEM, N = 10 pairs, P<0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP(9K) and renal CaBP(28K) content was diminished in the SHR: 21.0 ± 0.80 vs. 29.9 ± 2.19 μg/mg protein, N = 6 pairs, P<0.01 for duodenum, and 4.47 ± 0.39 vs. 7.67 ± 0.54 μg/mg protein, N = 6 pairs, P<0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.