It has been shown that red blood cell Li/Na exchange, also called countertransport (Li/Na CTT) is increased in patients with insulin dependent diabetes mellitus (IDDM) with clinical or subclinical nephropathy and elevated blood pressure. Because recent experimental evidence confirms that red cell Li/Na CTT is a mode of functioning of the Na/H exchange (Na/H CTT), we have measured both transport modes in 23 IDDM (16 hypertensive and seven normotensive) and in eight normotensive controls with normal glucose tolerance. Na/H and Li/Na CTT were significantly increased in hypertensive compared to normotensive diabetics and controls. Na/H CTT was 78 +/- 28 mmol/L cell/h in hypertensive IDDM, 50 +/- 21 in normotensive IDDM, and 55 +/- 24 in the controls. Li/Na CTT was 0.37 +/- 0.13 mmol/L cell/h, 0.27 +/- 0.10, and 0.25 +/- 0.11, respectively. Na/H and Li/Na CTT were significantly correlated (r = .38, P less than .05). The proximal tubule sodium reabsorption, measured as the fractional Li+ reabsorption, was significantly correlated to red cell Na/H CTT (r = .38, n = 29, P less than .05), but not to the Li/Na CTT (r = .21, n = 29). In conclusion this work confirms that Na/H and Li/Na CTT are function modes of the same transporter and that an increased activity of Na/H CTT might play a role in the blood pressure increase in IDDM.