The in vivo demyelinating capacity of sera from 27 patients with Guillain-Barré syndrome (GBS) and 47 other individuals was studied by intraneural injection into rat sciatic nerves. The morphological features of the nerves in cross section taken just proximal to the site of needle insertion was assessed 48 hours after injection and the extent of demyelination was quantitated. All 27 GBS serum samples were obtained in the first three weeks of clinical disease. Of these, 11 (41%) produced demyelination. Demyelinative activity of GBS sera correlated only with severity of clinical disease (p less than 0.01). The extent of demyelination after intraneural injection of human sera was less intense on average than that produced by sera from animals with experimental allergic neuritis. Three of 40 (7.5%) sera obtained from normal subjects and patients with other neurological diseases also caused in vivo demyelination, although the activity was weaker and occurred less often than with GBS serum.