JOHANNESBURG, AUG. 21 -- Mine security guards opened fire on striking black miners today, killing one and seriously wounding more than 20 others, in a 90-minute battle that company and union officials described as the most serious clash yet in the increasingly bitter strike at South Africa's gold and coal mines.

A mob of 250 striking miners, armed with clubs and spears, drugged with narcotics and anointed by a tribal witch doctor with a potion to protect them against bullets, were attacking other miners defying an industrywide strike when the guards opened fire, according to Gold Fields of South Africa Ltd.

But the National Union of Mineworkers said that the mine security force had assaulted miners who had joined its strike and refused to go to work last night at the Libanon gold mine, about 40 miles southwest of Johannesburg.

Four thousand miners were fired by the giant Anglo American Corp. at another mine today as the mining companies adopted a tougher approach to the strike, now ending its second week. More than 10,000 workers have now been fired, mostly by Anglo American, in what the union called "a desperate attempt by management to break the strike."

Nearly 19,000 other strikers at six more mines were told by Anglo American, the hardest hit of the mining companies, that they would also be dismissed if they did not resume work Monday, and 24,000 have been warned by the General Mining Union Corp. that they face "disciplinary actions" if they do not return next week.

A bus carrying about 100 strikers and their relatives home from a mine complex in the Orange Free State crashed into a mountain wall early Friday, killing 24 persons and injuring 49. The accident occurred in a remote area between Queenstown and Fort Beaufort about 400 miles south of Johannesburg.

"The strike is really beginning to hurt, and the mine owners are panicking," Marcel Golding, the union's assistant general secretary, commented today. "By firing 30,000, 40,000 or 50,000 workers, they believe they can intimidate 300,000 others. By shooting some of us, they think they can cow the rest. . . But their actions are only hardening our resolve."

According to the union, about 340,000 miners are on strike at 46 gold and coal mines in support of their demand for a 30 percent across-the-board pay increase as well as improved benefits and better working conditions.

The Chamber of Mines, which represents South Africa's six major mining companies, says that only 230,000 miners are on strike at 29 mines. The companies unilaterally implemented pay raises ranging from 15 percent to 23 percent in July and have since refused to discuss wages, but they say that other issues remain open for negotiation.