The adsorption of nefopam hydrochloride to two different charcoals was studied in vitro at pH 1.2 and 7.4. Both forms of activated charcoal effectively adsorbed nefopam, but the adsorption was significantly (p less than 0.001) more complete to PX-21 than to Norit A and the neutral pH favored adsorption over the acid pH. The unadsorbed fraction increased steeply when the charcoal-to-nefopam ratio was decreased below 5. In mice, the administration of Norit A and PX-21 (1700 mg/kg) significantly (p less than 0.001) increased the acute LD50 of nefopam hydrochloride, by 4.3 fold and 5.8 fold, respectively. The calculated amounts of free drug in the gastrointestinal tract are in good agreement with the observed LD50 values without charcoal when the free fractions at pH 1.2 and the corresponding charcoal-to-nefopam ratios in vitro are used in the calculations. The antagonism of charcoal to nefopam toxicity was confirmed in rats, too. At charcoal-to-nefopam ratios higher than those used in the present study, an even more effective reduction of toxicity is obvious. Therefore, immediate oral administration of a high dose (50-100 g) of activated charcoal is highly recommended to prevent nefopam absorption in acute intoxications in man, too.