In order to elucidate the diagnostic significance of urinary apolipoprotein H (apo H), known as beta 2-glycoprotein I, urinary apo H levels were measured by a non-competitive enzyme immunoassay in diabetics without hypertension and Albustix-positive proteinuria. The relationships between urinary apo H levels and urinary albumin (Alb) levels as well as clinical profiles in diabetics were investigated. The mean urinary apo H level in 45 diabetics was 264.2 +/- 189.5 micrograms/g.cr, and significantly higher than that in 41 healthy subjects (120.6 +/- 84.8 micrograms/g.cr, p < 0.01). Diabetics were classified into three groups based on urinary Alb levels; 17 group I patients with normoalbuminuria (U-Alb < 15mg/g.cr), 12 group II patients, whose urinary Alb levels were in between normo- and microalbuminuria (15 < or = U-Alb < 30mg/g.cr) and 16 group III patients with microalbuminuria (30 < U-Alb < or = 300mg/g.cr). The mean urinary apo H level in group I patients, who were regarded as without nephropathy, was 199.2 +/- 109.0 micrograms/g.cr, significantly higher than that in normal subjects (p < 0.01). The mean urinary apo H levels in group II and III were 271.4 +/- 177.1 and 327.8 +/- 246.1 micrograms/g.cr, respectively. These values were also higher than in normal subjects (both of p < 0.01). Urinary apo H levels correlated positively with urinary levels of glycosaminoglycan (r = 0.382, n = 45, p < 0.01), which was regarded as an indicator of the anion loss from glomerular basement membrane to urine, and with urinary N-acetyl-beta-D-glucosaminidase activities (r = 0.378, n = 37, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)