Respiratory failure is a serious feature of sepsis, and animal studies suggest this is due to skeletal muscle dysfunction (e.g Hussain et al, 1985). The effects of sepsis on human muscle contractility are unclear, and patient studies are likely to be confounded by malnutrition and therapeutic neuromuscular blockade. This Local Research Ethics Committee-approved study used an in vivo sepsis model to assess the effects of this, and the resulting systemic inflammatory response, on quadriceps contractile function. Eight healthy males, mean (SD) age 32.0 (4.4) yr were examined twice, in random order and 2 weeks apart. On one occasion they received 4 ng/kg i.v E.coli lipopolysaccharide (LPS), and on the other the same volume of i.v sterile normal saline. Pulse rate, rectal temperature and oxygen consumption (VO₂), and arterialised venous plasma concentrations of cortisol, growth hormone (GH), IL-6 and TNF-α were monitored/measured hourly for one hour before and 6 hours following i.v LPS/saline. Also assessed hourly were isometric quadriceps contractile properties: maximum voluntary contractile force (MVC), and 10:50 and 20:50 Hz force ratios and maximum relaxation rate (MRR) determined from computer-controlled electrically stimulated contractions (6s trains comprising 10, 20 and 50Hz, arranged contiguously). Statistical comparisons used repeated measures ANOVA and, where treatment/time interactions were apparent, post-hoc Student’s t-test using Bonferroni corrections for multiple comparisons.LPS caused fever, tachycardia and increases in plasma cortisol, GH, IL-6 and TNF-α concentrations (saline/LPS comparisons made at peak LPS-induced change): pulse rate 64.4 (8.8) vs 90.6 (10.3) bpm, core temperature 36.4 (0.2) vs 37.8 (0.3) ^oC, VO₂ 120.2 (8.3) vs 145.9 (18.7) ml/min/m²,cortisol 159.8 (46.6) vs 721.6 (105.6) nmol/L, IL-6 11.0 (8.7) vs 1074.0 (754.9) pg/mL, GH 4.8 (6.7) vs 33.6 (19.7) mU/L and TNF-α 13.9 (7.7) vs 960.7 (589.6) pg/mL, p<0.01 for each comparison. LPS had no effect on quadriceps contractile performance (saline/LPS comparisons shown made at 3 hours): MVC 750 (80.1) vs 741.8 (82.5) N, 10:50 ratio 27.3 (7.3) vs 29.7 (4.2), 20:50 ratio 72.4 (7.8) vs 73.4 (8.9) and MRR 4.71 (0.56) vs 5.00 (0.73) % per 10ms, p>0.05 for each comparison. The LPS doses given were small, compared with those previously given to animals (e.g Hussain et al), but the systemic physiological effects were large and highly significant. These results suggest that sepsis-induced neuromuscular and/or contractile dysfunction may only occur if sepsis is intense or prolonged.