Dialysis patients exposed to high aluminum (Al) dialysate develop a microcytic anemia which is reversed by deionization (DI) of the dialysate. Because DI removes substances in addition to Al which are known to cause anemia, these experiments were undertaken to determine if Al causes anemia and if the anemia of uremia can be enhanced by Al. Four groups of rats were studied: sham control (A) N = 6; uremic control (B) N = 6; Al-loaded non-uremic (C) N = 7; and Al-loaded uremic (D) N = 5. Aluminum treatment was 1 mg Al intraperitoneally daily for 6 weeks. Uremic rats (B+D) were 1 5/6 nephrectomized; non-uremic (A+C) were sham-operated. Blood samples (200 microliter) were obtained prior to (C1) and weekly during treatment (T1 to T6) and analyzed by Coulter Counter. No significant difference in hemoglobin (Hb), hematocrit (Hct), or mean cell volume (MCV) was noted at C1 X At T3, MCV of Al-treated rats (C+D) was significantly less than sham control (A) (55.1 +/- 0.5 and 53.0 +/- 0.8 vs. 60.8 +/- 1.5 mu3, P less than 0.05). At T6, MCV, Hb, and Hct of Al-loaded uremic rats (D) (49 +/- 0.5 mu3; 11.8 +/- 0.5 g/dl; 25.1 +/- 2%) were significantly less than both A (58.6 +/- 1.3 mu3; 16.1 +/- 0.4 g/dl; 44.8 +/- 0.3%) and B (58.7 +/- 1.4 mu3; 13.8 +/- 0.4 g/dl; 33.6 +/- 0.5%) (P less than 0.05) and MCV, Hb, and Hct of Al-loaded non-uremic rats (C) (51.7 +/- 1.7 mu3; 12.6 +/- 0.3 g/dl; 29.4 +/- 1.5%) was significantly less than A (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)