Background: Gram stain is used to detect urethral inflammation, suggestive of infection, in men and guide therapeutic decisions. In the absence of signs, symptoms, or polymorphonuclear leukocytes (PMNs) on urethral Gram stain, treatment and sometimes testing is deferred. Goal: Determine the proportion of men with chlamydia or gonorrhea diagnosed by nucleic acid amplification testing (NAAT) or culture who lack Gram stain evidence of inflammation and compare their clinical characteristics to men with inflammation. Methods: Records from 2629 men presenting for routine sexually transmitted disease care with urethral PMN count and NAAT data were retrospectively analyzed. A subpopulation tested by NAAT and culture was analyzed. Men receiving antibiotics within the prior month or those reporting a sexual partner with trichomoniasis were excluded. Results: Among 2266 eligible men, 353 (16%) had chlamydia and 462 (20%) had gonorrhea. Among chlamydia-infected men, PMNs per oil-immersion field (oif) on Gram stain were ≥5 in 291 (82%), 1 to 4 in 20 (6%), and none in 42 (12%). In men with gonorrhea, PMNs/oif were ≥5 in 433 (94%), 1 to 4 in 6 (1%), and none in 23 (5%). Urethral symptoms, discharge, and/or as PMNs/oif were absent in 47 (13%) and 22 (5%) of chlamydial and gonococcal infections, respectively (including no PMNs/oif and 1-4 PMNs/oif). None of these 47 chlamydial-infected men and only 4 of 22 men with gonorrhea received therapy at the time of initial examination. Conclusions: Twelve percent of chlamydial and 5% of gonococcal infections had no Gram stain evidence of urethral inflammation. Absence of symptoms and discharge is not uncommon in chlamydial infection detected by NAAT, and without testing, many infections will go untreated, furthering the possibility of complications or partner transmission. Copyright © 2005, American Sexually Transmitted Diseases Association. All rights reserved.