Dehydration and sweat sodium losses have been implicated in exercise associated muscle cramps (EAMC). PURPOSE: To compare blood electrolytes, hemoglobin (Hb), hematocrit (Hct) and serum osmolality (Osms) during EAMC to those same measures immediately after IV treatment when EAMC are alleviated. Secondly, to compare percent change in body mass (%ΔBM) in players with EAMC to that of matched players without EAMC (No-EAMC) after the same practice. METHODS: Eleven NFL players who sustained EAMC on 13 occasions during training camp with: age = 25 ±2 yrs, mass = 106.6 ± 16 kg, ht = 188.6 ± 6 cm and BSA = 2.33 ± 0.19m2 participated. Ten cc of blood was drawn via 18 gauge catheter during EAMC. After IV treatment with 1 - 2 L of 9% saline and I L of ½ saline and 5% dextrose, 3 cc of blood was discarded and a second blood sample was drawn. Immediately after each sample was drawn the blood was analyzed for sodium (Na+), potassium (K+) and chloride (Cl-), by ion selective electrode, Hct (microhematocrit technique) and Hb (Hb meter) and 8 cc was placed in serum tubes and spun for assessment of Osms by osmometry. Paired t-tests were used to compare pre and post IV blood measures. EAMC players and a second group of players matched by mass, height, BSA and position (No-EAMC) were weighed pre and post practice and %ΔBM was calculated. RESULTS: Compared with pre IV there were lower post IV blood measures of Na+ (142 ± 2 vs. 139 ± 2.4mmol/l, p<.001), Hb (16.6±1.3 vs. 13.5±1 mg/dl, p<.0001), Hct (51± 2% vs. 42.5 ± 2% p <.0001) and Osms (293 ± 6 vs. 289 ± 6 mOsm/kg, p <.01). Conversely, Cl- increased post IV (99.8 ± 3 vs. 103 ± 3 mmol/l, p<.0001) and on 6 occasions was clinically low, < 100 mmol/l during EAMC. There were no differences between EAMC and No-EAMC (mass = 106 ± 17 kg, ht = 187 ± 7 cm and BSA = 2.31 ± 0.22 m2) in physical characteristics or in %ΔBM during practice (2.0 ± 1.1% vs. 1.8 ±.7%). CONCLUSIONS: Low blood chloride appears to be an important factor in EAMC, likely indicating an abnormal anion gap resulting from respiratory or metabolic alkalosis. Strenuous exercise is linked to EAMC and hyperventilation. Hypochloridemia could reduce hyperpolarization of the alpha motor neuron promoting hyperexcitability. Importantly, EAMC occurred in players with mild %ΔBM (2%) which by itself appears to have little effect on EAMC as No-EAMC experienced the same %ΔBM during the same practices.